tbuckley/cabot-search huggingface dataset:
Desmocollin 3 (DSC 3) expression in different subtypes of non-small cell lung cancer.
Authors: Elena P. Ulianova, Oleg N. Stateshny, Aleksandr B. Sagakyants, Dmitry A. Kharagezov, Igor A. Leyman, Anton G. Milakin, Madina A. Gappoeva, Kristian D. Iozefi, Maksim N. Chernyak, Oksana G. Shulgina, Yuriy N. Lazutin, Elena A. Dzhenkova, Inna A. Novikova, Natalia N. Popova, Lyudmila Ya Rozenko
Journal: Journal of Clinical Oncology (2022)

e20513 Background: Currently, an active search is underway for additional markers that predict the risk of tumor progression based on the epithelial-mesenchymal transition (EMT). Desmocollin 3 (DSC 3), a member of the Cadherin superfamily and a cell adhesion marker, is one of the markers for this transition. The aim of our study was to evaluate the expression of DSC 3 as a prognostic factor in different subtypes of non-small cell lung cancer. Methods: The study included 12 patients with squamous cell lung cancer and 8 patients with lung adenocarcinoma, aged 49 to 76 years. Immunohistochemical study was performed on sections from paraffin blocks of tumors using polyclonal rabbit antibodies to Desmocollin 3 (Invitrogen) at a dilution of 1:300 and the UltraVision Quanto Detection System HRP DAB. The expression of DSC 3 was semiquantitatively analyzed according to the percentage of cells and the intensity of staining: 0; 1+ (weak); 2+ (moderate); 3+ (high). Expression was considered positive if the score was ≥2. The Mann-Whitney U-test, Pearson's χ² distribution, and Spearman's correlation coefficient were used for statistical analysis of the results. Results: The predominance of patients with DSC3+ tumors was noted in the group with squamous cell carcinoma (64%), while the majority of patients with adenocarcinoma had DSC3- tumors (71%). However, Pearson's χ² was not statistically significant. Differences in DSC 3 expression values by 1.3 times were insignificant (p = 0.082): Me = 40 [0-80] in squamous cell carcinoma, Me = 30 [0-65] in adenocarcinoma. The correlation analysis between the expression of this marker and the survival rate of patients also had no statistical significance (rs = 0.061 for squamous cell carcinoma and rs = 0.196 for adenocarcinoma, p &gt; 0.05). Conclusions: The immunohistochemical study revealed some specific features in the expression of DSC 3 in different subtypes of non-small cell lung cancer.
OTHR-01. Papillary tumor of pineal region rare pediatric CNS tumor: case series treated in King Fahad Medical City KFMC
Authors: Nahla Ali Mobark, Musa AlHarbi, Fahad Alotabi, Azhar Alshoumer, AbdulAziz Alsadi, Zaid G AlNaqib, Wafa Al Shakweer, Ali O Balbaid, Malak Abedalthagafi
Journal: Neuro-Oncology (2022)

Abstract Clinical behaviors, prognosis, and appropriate treatments of PTPR are not fully defined due to the rarity of these tumors. At diagnosis, PTPR may present with various clinical symptoms with obstructive hydrocephalus, as well as neurological signs including Parinaud’s syndrome. Radiological assessment of pineal region lesions is challenging with a wide range of potential differential diagnoses. PTPR typically presents as a heterogeneous, well circumscribed mass in the pineal region. we report 3 female pediatric cases of PTPR treated in our institution. Histological and immunohistochemical diagnosis was confirmed by analysis of genome-wide DNA methylation profiles. the first case presenting with spinal leptomeningeal dissemination with excellent tumor control with radiation therapy alone. The second patient had aggressive course with recurrent local tumor growth despite radiation therapy and 0repeated surgical resections and she responded well to Pineoblastoma like intensive chemotherapy6 repeats of alternating 4-week cycles A&amp;B : Cycle A: Cisplatin 90 mg/m2/day, day 1 of a &amp; oral Etoposide 35 mg/m2/day P.O. days 1-21 . Cycle B: Cyclophosphamide 1 g/m2/day, days 1 and 2, Vincristine 1.5 mg/m2, days 1, 8 . While the third patient after first near gross total surgical resection with no recurrence for 18 months without adjuvant therapy then she had local recurrence which was salvaged by second complete resection and focal radiation The proper therapeutic strategy for PTPR is not clearer and the clinical behavior of PTPRs can be compared to that of ependymoma with complete resection is the mainstay of treatment and we recommend that adjuvant therapies like radiation with or without or chemotherapy should be considered when complete surgical resection is not feasible. This case series expands on the available reports on the clinical presentations of PTPR and provides important information on the responses to different treatments modalities
18F-PSMA-11 Versus 68Ga-PSMA-11 Positron Emission Tomography/Computed Tomography for Staging and Biochemical Recurrence of Prostate Cancer: A Prospective Double-blind Randomised Cross-over Trial
Authors: Kathia De Man, Nick Van Laeken, Vanessa Schelfhout, Wolfgang P Fendler, Bieke Lambert, Ken Kersemans, Sarah Piron, Nicolaas Lumen, Karel Decaestecker, Valérie Fonteyne, Louke Delrue, Filip De Vos, Piet Ost
Journal: European Urology (2022)
Clinical impact of SARS-CoV-2 delta variant infection in tumor patients and the impact of vaccination on different cancer treatment regimens.
Authors: Louisa Hempel, Armin Piehler, Beate Gandorfer, Julia Veloso de Oliveira, Patrick Philipp, Sebastian Robert, Kleespies Axel, Cordula Schick, Bastian Fleischmann, Katrin Schweneker, Valeria Milani, Kristina Schenk, Florian Ebner, Lara Donhauser, Dietmar Zehn, Dirk Hempel
Journal: Journal of Clinical Oncology (2022)

e18750 Background: Data on SARS-CoV-2 infections in oncological patients in the outpatient settings are scarce. Methods: During the spread of the delta variant between April 2021 and September 2021, a total of 10.677 patients were tested for SARS-CoV-2 infection by RT-qPCR in seven outpatient clinics in Bavaria, Germany. Results: Within the tested patient cohort, 4.960 patients (46.5%) suffered from a malignant disease (74% solid tumors and 26% malignant hematological diseases). This group was compared with 5.717 patients (53.5%) without a malignant disease (33.1% with other hematological diseases and 66.9% patients without a hematological or oncological disease). During the observation period, 119 (2.4%) patients with malignancies were tested positive (88 patients with solid tumors; 31 patients with malignant hematological diseases) compared to 115 positive patients (2.0%) in the control group. 32 of 119 positively tested patients (26.9%) suffering from malignant disease required hospitalization and 9/32 patients (28.1%) died during the clinical course. Conclusions: These observations are in clear contrast to data from patients we evaluated during the pre-delta variants period between 15 and 26 April 2020 in the same seven outpatient clinics. In this period, a total of 1.227 patients were tested for SARS-CoV-2 by RT-qPCR. 78/1227 patients (6.3%) were tested positive in RT-qPCR and most showed mild symptoms of infection. None of the SARS-CoV-2 infected patients died. These data were analyzed when no vaccination was available. These data were evaluated during a period where no vaccine was available. Vaccination of patients with malignancies with BiontechPfizer's mRNA vaccines was started in April 2021. The response to the vaccine was tested by an antibody assay (Elecsys Anti-SARS-CoV-2 S-immunoassay, Roche) at the earliest four weeks after the second vaccination. To assess the response, we compared five patient cohorts: Patients who received (i) B cell depleting antibodies, (ii) checkpoint inhibitors (ICI), (iii) chemotherapy, or (iv) tyrosin kinase inhibitors (TKIs), and (v) healthy controls. The patients treated with ICI or TKI showed a comparable vaccination response to the healthy patients, while patients receiving Rituximab/Obinutuzumab showed no significant humoral vaccination response at all. The more severe disease course of patients infected by the SARS-CoV-2 delta variant compared to the initial waves of infections strongly underline the importance of vaccination in cancer patients.
Optimizing rural healthcare: A retrospective review of initial diagnostic workup for multiple myeloma or monoclonal gammopathy.
Authors: Jeremy Schmoyer, Tro Sekayan, Neychelle Rocca
Journal: Journal of Clinical Oncology (2022)

e18653 Background: An estimated 65 million people or approximately 20% of the United State residents live in rural areas based on the Census Bureau designation. As of December 31, 2021, 61.5% of the health professional shortage areas were designated in rural primary medicine. The Northern Arizona Healthcare (NAH) system is based in a rural area and experiencing shortages in both primary care and subspecialty physicians. This is making accurate and timely diagnostic studies key to facilitating early treatment. The objective of this study is to review whether complete diagnostic work up was performed for patients with suspected multiple myeloma (MM) or monoclonal gammopathy (MG) disorders prior to the oncology referral. The future goal of this study is to prompt further reviews and creations of order modules to help optimize healthcare for individuals in rural areas. Methods: This retrospective study included patients with the diagnosis of multiple myeloma or monoclonal gammopathy in the NAH system from 2015 to 2020. Data was reviewed to determine if serum protein electrophoresis (SPEP) with immunofixation was requested prior to oncology referral or at first oncology visit. Additionally, we evaluated if the urine protein electrophoresis (UPEP) order was requested on these visits as well. Results: The data consisted of 74 patients. On review, prior to oncology referral or at first oncology visit, only 18 patients (24%) had SPEP with immunofixation and UPEP ordered. 23 patients (31%) had SPEP orders only requesting additional immunofixation for further interpretation of data on future visits, and 47 patients (63%) were missing concurrent UPEP and SPEP orders. Conclusions: This retrospective study demonstrated that for patients with a confirmed final diagnosis of either MM or MG, 31% and 63% of patients had missing immunofixation and concurrent UPEP plus SPEP results respectively. The outpatient cerner system orders were adjusted to remove SPEP and UPEP only orders in the LabCorp and Senora Quest options. These were replaced with SPEP and UPEP with reflux to immunofixation orders. The goal of this adjustment is to prevent re-ordering of labs at initial oncology visit limiting cost burden and delay of diagnosis. In the future, patient care will be further optimized at NAH with the creation of an order set module. This module will include the complete lab workup required for multiple myeloma or monoclonal gammopathy with hematology/oncology referral and allow for further integration of non-oncology clinicians into care delivery.
Subgroup analysis in patients (pts) with non-squamous (N-Sq), EGFR-wild type (wt), second/third-line NSCLC from the global phase (Ph) 3 trial DUBLIN-3 (BPI-2358-103) with the plinabulin/docetaxel (Plin/Doc) combination versus Doc alone.
Authors: Baohui Han, Trevor Feinstein, Yuankai Shi, Michael Chen, Lan Huang, Ramon W. Mohanlal, Yan Sun
Journal: Journal of Clinical Oncology (2022)

9090 Background: With PD-1/PD-L1 inhibitors moving to first line in NSCLC, 2 nd /3 rd line NSCLC is a severe unmet medical need, dominated by docetaxel-based therapies with &gt; 40% severe neutropenia and limited survival. Plin, a novel immune-enhancing small molecule, enhances dendritic cell maturation and T-Cell proliferation. In the ITT population, the Plin/Doc combination had superior Efficacy (mOS; HR = 0.82, p = 0.0399), Safety (lower Gr3/4 AE rate/pt/year (yr); p = 0.038) and better Quality of Life (QTWiST; p = 0.026) versus (vs) standard of care (SoC) Doc alone in advanced and metastatic NSCLC pts in DUBLIN-3 (Han, ESMO 2021) who failed platinum therapy. Here we report on the N-Sq pts subgroup. Methods: DUBLIN-3(NCT02504489) was a randomized, single-blind (pts only), active controlled Ph3 study in 2 nd /3 rd line stage IIIB/IV, EGFR wt NSCLC pts with a measurable lesion (RECIST 1.1) in the lung, and ECOG ≤ 2, conducted in US, Australia and China. Pts (n = 559) were randomized 1:1 to Plin/Doc or Doc/Placebo (21-day (D) cycle (C)). Doc (75 mg/m 2 on D1 and Plin 30 mg/m 2 on D1 and D8 were given by IV infusion. A post-hoc analysis of median Overall Survival (mOS) and restricted mean survival time (RMST) from K-M curves, OS rate at 24,36 and 48 month (Mo), and grade 4 neutropenia (Gr4N) rates was performed for the N-Sq patients (n = 153 for Plin/doc and n = 178 for Doc). Results: Baseline characteristics were balanced between both groups. Primary and key secondary objectives in the ITT population were met (Han, ESMO 2021). Plin/Doc was well tolerated. Estimated Adverse Event Rate per Year [95% CI] was 1.43 [1.13,1.81] for Plin/Doc versus 2.77 [2.33,3.28] for Doc alone (p &lt; 0.001). The median OS benefit is 2.6 months (p = 0.023). The table below summarizes the results for the N-Sq subgroup. Conclusions: The addition of Plin to Doc was superior to SoC Doc alone for efficacy and safety in the clinically relevant subgroup of non-squamous EGFR-wild type, 2 nd /3 rd line NSCLC pts. Clinical trial information: NCT02504489. [Table: see text]
Efficacy of next line of therapy after treatment with lenvatinib (LEN) in combination with pembrolizumab (pembro) versus treatment of physician’s choice (TPC) in patients (pts) with advanced endometrial cancer (aEC): Exploratory analysis of Study 309/KEYNOTE-775.
Authors: Vicky Makker, Nicoletta Colombo, Alessandro Santin, David Scott Miller, Keiichi Fujiwara, Sandro Pignata, Isabelle Laure Ray-Coquard, Yong Man Kim, Eva M. Guerra, Jie Huang, Gianmaria Barresi, Jodi McKenzie, Domenica Lorusso
Journal: Journal of Clinical Oncology (2022)

5587 Background: In the multicenter, open-label, randomized, phase 3 Study 309/KEYNOTE-775, LEN + pembro had significant PFS and overall survival benefits, and improved objective response rate vs TPC in pts with aEC following systemic platinum-based treatment (Makker 2022, NEJM). These results were seen in all-comer pts and in pts with DNA mismatch repair proficient (pMMR) disease. Here, we assessed PFS on next line of therapy (PFS2) of each arm. Methods: Pts with aEC and 1 prior platinum-based chemotherapy regimen (or up to 2 if 1 was given in neoadjuvant/adjuvant setting) were randomized (1:1) to receive LEN 20 mg orally QD + pembro 200 mg IV Q3W or TPC (doxorubicin at 60 mg/m 2 IV Q3W or paclitaxel at 80 mg/m 2 IV QW [3 weeks on; 1 week off]). Randomization was stratified by MMR status (determined centrally); pts with pMMR tumors were further stratified by Eastern Cooperative Oncology Group performance status, geographic region, and history of pelvic radiation. In this prespecified exploratory analysis, PFS2 (defined as the time from randomization to disease progression on next line of treatment or death, whichever came first) was analyzed per investigator assessment in the pMMR and all-comer populations. Results: 827 Pts (pMMR, n=697; MMR deficient [dMMR], n=130) were randomized to LEN + pembro (n=411) or TPC (n=416). At data cutoff (October 26, 2020), 567 pts (LEN + pembro, n=282; TPC, n=285) had discontinued study treatment and 315 (LEN + pembro, n=115; TPC, n=200) had received a subsequent systemic anticancer therapy (Table): most commonly doxorubicin (n=58) in the LEN + pembro arm and paclitaxel (n=57) in the TPC arm. Median PFS2 was longer in the LEN + pembro arm vs the TPC arm in the pMMR population (14.4 vs 9.8 mo; HR 0.62, 95% CI 0.50–0.75) and in the all-comer population (16.0 vs 9.5 mo; HR 0.56, 95% CI 0.46–0.67). Additionally, the PFS2 rate at 6 months favored LEN + pembro vs TPC in the pMMR population (82.0% vs 74.8%) and in the all-comer population (81.7% vs 72.5%). Conclusions: Clinically meaningful improvements in PFS2 were seen in the LEN + pembro group compared with TPC in pMMR and all-comer pts. Clinical trial information: NCT03517449. [Table: see text]
Tumor size and WIT are involved in the increase of contralateral kidney function after RAPN: Evaluation by MAG3
Authors: K. Yoshinaga, M. Araki, K. Edamura, T. Sekito, Y. Maruyama, T. Sadahira, T. Sako, Y. Kobayashi, T. Watanabe, Y. Nasu
Journal: European Urology (2022)
HGG-45. Characterization of spinal diffuse midline gliomas, H3 K28M-mutant
Authors: Lotte Stegat, Christian Thomas, Leonille Schweizer, Sina Neyazi, Lara Pohl, Stephan Frank, Mario M Dorostkar, Ulrich Schüller, Annika K Wefers
Journal: Neuro-Oncology (2022)

Abstract Diffuse midline gliomas (DMGs) are malignant gliomas that arise in the midline structures of the central nervous system. Due to their aggressive and diffuse growth and a two-year survival rate of less than 10%, DMGs are assigned to CNS WHO grade 4. Depending on the localization, median age of patients is about 11‒20 years. Genetically, most tumors are defined by a K28M-mutation in one of the highly homologous genes encoding histone protein H3. Since DMGs most frequently occur in pons and thalamus, comparatively little is known about spinal DMGs. Therefore, we histologically, molecularly, and clinically characterized spinal DMGs and analyzed, in which aspects they differ from DMGs of other localizations. Our cohort currently consists of 25 spinal DMGs and 40 pontine/thalamic reference cases. Histological, immunohistochemical and molecular analyses (DNA methylation, DNA panel sequencing) were done from FFPE tissue. Spinal DMGs were histologically very heterogeneous, both regarding different areas of single tumors as well as in comparison to other spinal and reference cases. First cluster analyses of DNA methylation data indicated a separation into three main clusters enriched for pontine, thalamic or spinal cases. The cluster enriched for spinal cases contained many tumors from elderly patients. Overall, mean age of patients with spinal DMGs was 28 years. Patients were significantly older than those with pontine DMGs. 19/20 spinal DMGs were H3-3A K28M-mutant, while one tumor had an H3-2B mutation. 4/19 (21%) spinal DMGs had mutations in FGFR1, and 6/10 (60%) in NF1. Three tumors had KRAS or BRAF mutations. In summary, first analyses suggest slight histological differences of spinal DMGs compared to DMGs of other localizations. Preliminary cluster analyses of DNA methylation data showed an enrichment of clusters for different localizations. About one third of spinal DMGs had mutations in a gene associated with the MAPK-signaling pathway.
Assessment of predictors of renal cell carcinoma progression after nephrectomy at short and intermediate term follow-up and their implication on surveillance protocols
Authors: D. Perri, C. Palumbo, M. Zacchero, M. Billia, D. D'Agate, A. Abdulvagabov, G. Bondonno, A. Volpe
Journal: European Urology (2022)
Liver ductal organoids reconstruct intrahepatic biliary trees in decellularized liver grafts
Authors: Katsuhiro Tomofuji, Ken Fukumitsu, Jumpei Kondo, Hiroshi Horie, Kenta Makino, Satoshi Wakama, Takashi Ito, Yu Oshima, Satoshi Ogiso, Takamichi Ishii, Masahiro Inoue, Etsuro Hatano
Journal: Biomaterials (2022)
A phase 1 trial of the PARP inhibitor fuzuloparib in combination with the anti-angiogenic apatinib in recurrent ovarian or triple-negative breast cancer.
Authors: Huiping Li, Jiayang Zhang, Rutie Yin, Nan Song, Youzhong Zhang, Yu Zhang, Keqiang Zhang, Hongming Pan, Ke Wang, Ge Lou, Li Guiling, Ben Zhang, Quanren Wang, Yunong Gao
Journal: Journal of Clinical Oncology (2022)

5539 Background: The combination of an anti-angiogenic agent with a poly (ADP-ribose) polymerase (PARP) inhibitor has demonstrated improved clinical outcomes as treatment/maintenance treatment in gynecological cancers. Here we aimed to characterize the safety profile and recommended phase 2 dose (RP2D) of the combination of fuzuloparib (formerly fluzoparib), a PARP inhibitor, and apatinib, a VEGFR inhibitor in recurrent ovarian cancer (OC) or triple-negative breast cancer (TNBC). Methods: This was a dose-escalation and PK-expansion phase 1 trial conducted in China. Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer or metastatic TNBC were eligible. No prior PARP/VEGFR inhibitors were allowed. The study used a standard 3+3 dose-escalation design, with additional patients (a total of 8-12 patients per dose level) enrolled for PK assessment. Patients received orally a single dose of fluzoparib on D1 and apatinib on D4, followed by continuous dosing of fluzoparib (bid) plus apatinib (qd) starting on D8. Endpoints were RP2D, safety, PK, and anti-tumor activity. Results: Between 03/17/2017 and 03/02/2021, 52 patients (30 OC, 22 TNBC) were enrolled to 7 dose levels (up to fuzuloparib 100 mg plus apatinib 500 mg). A total of 2 DLTs occurred: grade 4 decreased white blood cell count (WBC)/febrile neutropenia (fuzuloparib 100 mg plus apatinib 250 mg) and grade 4 thrombocytopenia (fuzuloparib 100 mg plus apatinib 375 mg). No maximum tolerated dose was reached. The most common treatment-related grade ≥3 toxicities included hypertension, anemia/decreased hemoglobin, thrombocytopenia, and decreased WBC. In PK analysis, steady-state plasma concentrations of apatinib was decreased when combined with fuzuloparib, as compared with apatinib alone. Higher dose of apatinib in combination with fuzuloparib 100 mg was associated with higher exposure and improved clinical activity. The ORR was 44% (95% CI, 32-58; OC, 60% [95% CI, 42-75]; TNBC, 23% [95% CI, 10-43]) across all dose levels and 62.5% (95% CI, 31-86) at fuzuloparib 100 mg plus apatinib 500 mg (all OC), which was determined to be the RP2D. Conclusions: Fuzuloparib plus apatinib has acceptable safety in patients with recurrent ovarian cancer and triple-negative breast cancer. With the promising clinical activity observed in ovarian cancer, this combination is warranted to be further explored as a potential alternative to chemotherapy. Clinical trial information: NCT03075462.